Test Summary
Culture, Blood With Reflexes
Test code: 13954
Clinical use
- Diagnose bacteremia and guide treatment selection
Clinical background
Bacterial bloodstream infections can progress to sepsis, a life-threatening organ dysfunction caused by a dysregulated host response to infection.1 Prompt treatment with appropriate antimicrobials is critical for managing infections and sepsis1,2; the sooner appropriate treatment begins, the better the chance of patient survival.1,3
Laboratory testing guides appropriate treatment by identifying the causative microorganisms and their antimicrobial susceptibilities, but test methods and turnaround times vary.3,4 Conventional testing methods, which involve subculturing the microorganism, can take several days.3 Rapid testing methods, such as molecular panels, detect organism-specific DNA in <3 hours.5,6 Rapid methods can also test for resistance markers, which are genes or enzymes that allow an organism to be resistant to certain antimicrobial treatments.3,5,6
Using both rapid and conventional testing methods is the standard of care for bloodstream infections3 and, when combined with support from an antibiotic stewardship program, is recommended by the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA).7 This approach can improve clinical outcomes for bloodstream infections. A meta-analysis found that rapid testing methods are associated with shorter time to appropriate treatment (averaging about 5 fewer hours), shorter hospital stays (averaging about 2.5 fewer days), and lower mortality risk (odds ratio, 0.64) than conventional methods.8
Rapid molecular tests are highly accurate for identifying the organisms and resistance markers they target, showing 85% to 100% positive percent agreement and 82% to 100% negative percent agreement with conventional methods.4-6 However, accuracy may be lower when multiple microorganisms are present3,4; molecular tests may only correctly identify 50% to 75% of microorganisms in polymicrobial cultures, compared to >90% in monomicrobial cultures.9
The Culture, Blood with Reflexes test (test code 13954) uses rapid and conventional testing methods to detect, identify, and determine the antimicrobial susceptibilities of pathogenic bacteria in the bloodstream.3,5,6 The test begins with a blood culture to test for organism growth. If growth is detected, reflex tests are performed to identify the organism and determine its antimicrobial susceptibilities. Reflex testing includes
- A Gram stain to classify the organism
- A rapid molecular identification panel to test for the presence of select bacteria and resistance markers (results available within 3 hours of blood culture positivity)
- Conventional (culture-based) organism identification and antimicrobial susceptibility testing (results available within 1 to 2 days of blood culture positivity)
Reflex tests are performed at additional charge and associated with additional CPT codes.
Results of the Gram stain determine which of 2 molecular identification panels (gram-positive or gram-negative) are tested. The gram-positive panel tests for 12 bacterial targets and 3 resistance markers; the gram-negative panel tests for 8 bacterial targets and 6 resistance markers (Table 1). Collectively, the panels account for approximately 80% of the pathogens most commonly responsible for bloodstream infections.10,11
Table 1. Bacteria and Resistance Markers Included in Molecular Identification Panelsa
|
Bacteria |
Resistance markers |
Gram-positive panel |
|
|
Gram-negative panel |
|
|
| a | Individual panel components cannot be ordered separately. |
| b | These bacterial targets are identified to the genus level. |
| c | Tested only if S aureus or S epidermidis are detected. |
| d | Tested only if E faecalis or E faecium are detected. |
| e | The test cannot distinguish between E coli and Shigella species; detection of either is reported as "E coli." |
Individuals suitable for testing
- Patients with suspected bacteremia
Methods
- Blood culture: culture using automated continuous monitoring system
- Gram stain: microscopic examination
- Molecular identification panel: DNA hybridization microarray
- Conventional identification and susceptibility testing: varies
Interpretive information
Results of the initial blood culture indicate whether organism growth was detected (positive) or not detected (negative) in the specimen.
Results of the molecular identification panel include the organism(s) detected and, if applicable, whether associated resistance markers were detected or not detected. An organism result of “not detected” indicates that none of the bacterial targets tested were detected. Because the panel can only detect the organisms it targets (Table 1), infection or coinfection with an untargeted organism cannot be ruled out.4
Detection of a resistance marker may predict that the associated organism will be resistant to certain antibiotics (Table 2). However, the predictive value of resistance markers varies:
- Gram-positive resistance markers (mecA and vanA/B) have high predictive value because they are the predominant mechanisms for certain kinds of antibiotic resistance in these organisms.3,11,12 Therefore, in most cases, the presence or absence of mecA or vanA/B can reliably predict resistance or susceptibility to the associated antibiotics.3
- Gram-negative organisms have multiple resistance mechanisms, not all of which are detectable by this test.3,5,11 Additionally, gram-negative resistance markers may be present but unexpressed or expressed at levels too low to cause resistance.3,11 Therefore, the presence or absence of a resistance marker in a gram-negative organism may not reliably predict antibiotic resistance or susceptibility.3,8,11
Due to the complexity of predicting phenotypic resistance from genotypic tests, the Clinical and Laboratory Standards Institute (CLSI) and IDSA/SHEA recommend that treatment changes based on molecular test results be made with guidance from an antimicrobial stewardship team.3,7
Table 2. Interpretation of Molecular Resistance Marker Results
Organism |
Resistance marker |
Interpretation5,6,11,13 |
S aureus or |
mecA detected |
|
mecA not detected |
|
|
E faecium or |
vanA detected |
|
vanB detected |
|
|
vanA and vanB not detected |
|
|
Any gram-negative organism |
CTX-M detected |
|
CTX-M not detected |
|
|
Any gram-negative organism |
KPC, OXA, NDM, VIM, or IMP detected |
|
KPC, OXA, NDM, VIM, and IMP not detected |
|
| IMP, imipenem-resistant Pseudomonas; KPC, Klebsiella pneumoniae carbapenemase; NDM, New Delhi metallo-β-lactamase; OXA, oxacillinase; VIM, Verona integron-encoded metallo-β-lactamase. |
Results of conventional organism identification and antimicrobial susceptibility testing include the organism(s) detected and, for each organism-antimicrobial combination tested, minimal inhibitory concentrations and corresponding interpretations (susceptible, resistant, or intermediate). Interpretations are defined as follows13:
- Susceptible: The organism is inhibited by standard dosing of the drug, indicating that the drug is likely to be clinically effective.
- Resistant: The organism is not inhibited by standard dosing of the drug, indicating that the drug is not likely to be clinically effective.
- Intermediate: The organism is less likely to be inhibited by standard dosing of the drug than a susceptible organism is, indicating that the drug may or may not be clinically effective.
References
- Tang F, Yuan H, Li X, et al. Effect of delayed antibiotic use on mortality outcomes in patients with sepsis or septic shock: a systematic review and meta-analysis. Int Immunopharmacol. 2024;129:111616. doi:10.1016/j.intimp.2024.111616
- Briggs N, Campbell S, Gupta S. Advances in rapid diagnostics for bloodstream infections. Diagn Microbiol Infect Dis. 2021;99(1):115219. doi:10.1016/j.diagmicrobio.2020.115219
- Clinical and Laboratory Standards Institute. Principles and procedures for blood cultures, 2nd edition. CLSI guideline M47. 2022.
- Dunbar SA, Gardner C, Das S. Diagnosis and management of bloodstream infections with rapid, multiplexed molecular assays. Front Cell Infect Microbiol. 2022;12:859935. doi:10.3389/fcimb.2022.859935
- VERIGENE® Gram-Negative Blood Culture Nucleic Acid Test (BC-GN). Package insert. Luminex; 2020.
- VERIGENE® Gram-Positive Blood Culture Nucleic Acid Test (BC-GP). Package insert. Luminex; 2020.
- Barlam TF, Cosgrove SE, Abbo LM, et al. Implementing an antibiotic stewardship program: guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America. Clin Infect Dis. 2016;62(10):e51-e77. doi:10.1093/cid/ciw118
- Timbrook TT, Morton JB, McConeghy KW, et al. The effect of molecular rapid diagnostic testing on clinical outcomes in bloodstream infections: a systematic review and meta-analysis. Clin Infect Dis. 2016;64(1):15-23. doi:10.1093/cid/ciw649
- Freiberg JA, Deri CR, Nesbitt WJ, et al. Identification and antibiotic susceptibility patterns of clinical blood culture isolates not identified by a rapid microarray diagnostic system. Microbiol Spectr. 2021;9(1):e0017521. doi:10.1128/spectrum.00175-21
- Verway M, Brown KA, Marchand-Austin A, et al. Prevalence and mortality associated with bloodstream organisms: a population-wide retrospective cohort study. J Clin Microbiol. 2022;60(4):e0242921. doi:10.1128/jcm.02429-21
- Banerjee R, Patel R. Molecular diagnostics for genotypic detection of antibiotic resistance: current landscape and future directions. JAC Antimicrob Resist. 2023;5(1):dlad018. doi:10.1093/jacamr/dlad018
- Yee R, Bard JD, Simner PJ. The genotype-to-phenotype dilemma: how should laboratories approach discordant susceptibility results? J Clin Microbiol. 2021;59(6):e00138-20. doi:10.1128/jcm.00138-20
- Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing, 34th edition. CLSI guideline M100. 2024.
Content reviewed 5/2026
13954 - Culture, Blood with Reflexes
Bacterial sepsis constitutes one of the most serious infectious diseases and requires rapid diagnosis and timely antimicrobial therapy. Blood culture remains the cornerstone for detecting bacterial bloodstream infection, while the addition of NAATs can provide earlier organism identification and selected resistance marker detection to help guide treatment decisions [3,4]. This approach supports earlier optimization of antimicrobial therapy, improved stewardship, and faster clinical response.
NAATs remain dependent on organism growth in culture. They do not detect pathogens or identify resistance markers that are not targeted by this test or are outside of the limit of detection [3]. Conventional culture for organism recovery, identification, and full phenotypic suspectibility testing cannot be replaced by NAATs.
The results of NAATs should be interpreted in the context of Gram stain and culture results, and the overall clinical presentation and history [3]. A negative NAAT result does not rule out bacterial bloodstream infection or resistance mechanisms not targeted by the assay [4].
The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.
References
1. VERIGENE® Gram-Negative Blood Culture Nucleic Acid Test (BC-GN). Package insert. Luminex; 2020.
2. VERIGENE® Gram-Positive Blood Culture Nucleic Acid Test (BC-GP). Package insert. Luminex; 2020.
3. CLSI. Principles and Procedures for Blood Cultures, 2nd edition. CLSI guideline M47. 2022.
4. She RC, Van TT. Multiplex Molecular Panels for Positive Blood Cultures. In: ClinMicroNow. John Wiley & Sons Inc; 2020. Accessed April 7, 2026. doi.org/10.1002/9781683670438.cmph0051
Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.
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